Jürgen K. Rockstroh, MD, provides an update on the importance of HCV screening and the latest emerging treatment options for patients with HCV/HIV coinfection.
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Best Practices in the Management of HCV/HIV Coinfection: Optimizing Treatment Success.2014
1. Jürgen K. Rockstroh, MD
Professor of Medicine
University of Bonn
Bonn, Germany
Best Practices in the Management
of HCV/HIV Coinfection:
Optimizing Treatment Success
This program is supported by an educational grant from
2. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
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Best Practices in the Management of HCV/HIV Coinfection
Disclosures
Jürgen K. Rockstroh, MD, has disclosed that he has received
consulting fees from AbbVie, Bionor, Bristol-Myers Squibb,
Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Merck
Sharp & Dohme, Novartis, Pfizer, Roche, Tibotec/Janssen, Tobira,
and ViiV. He has also received research support from AbbVie and
Merck.
The following planners and managers, Edward King, MA;
Jenny Schulz, PhD; and Michael Westhafer, MD, hereby state
that they or their spouse/life partner do not have any financial
relationships or relationships to products or devices with any
commercial interest related to the content of this activity of any
amount during the past 12 months.
5. Please review the slide notes
for a discussion by Jürgen K.
Rockstroh, MD
7. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Background and Epidemiology
HIV accelerates the natural course of hepatitis C[1]
Successful antiretroviral therapy can slow fibrosis progression but not
back to the rate in HCV monoinfection[2]
Liver disease associated with HCV infection has become a leading
cause of morbidity and mortality among HCV/HIV-coinfected patients[3]
HIV/HCV epidemiology[4]
– Approximately 25% of HIV+ patients are coinfected with HCV
– Approximately 80% of HIV+ patients who inject drugs are coinfected with
HCV
– All patients with HIV infection should be tested for HCV
HIV+ patients are at 4.1 times the risk of HCV as HIV- patients[5]
1. Rockstroh JK, et al. Am J Gastroenterol. 1996;91:2563-2568. 2. Graham CS, et al. Clin Infect Dis.
2001;33:562-569. 3. Weber R, et al. Arch Intern Med. 2006;166:1632-1641. 4. CDC. HIV and viral
hepatitis. May 2013. 5. Yaphe S, et al. Sex Transm Infect. 2012;88:558-564.
8. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Sexual Transmission of HCV Among
HIV+ MSM: An Emerging Population
Reports of epidemic of sexually transmitted HCV among HIV+ MSM
– United States: 6-fold higher incidence rate in HIV+ vs HIV- MSM[6]
– Swiss HIV Cohort Study: HCV incidence increased 18-fold from
1998 to 2011[7]
– Sydney, Australia: 9% of HIV+ MSM coinfected with HCV vs 1.9%
HIV- MSM[8]
– Amsterdam, Netherlands: HIV/HCV coinfection prevalence
increased from 14.6% to 20.9% from 2000-2007[9]
Phylogenic analysis indicates HCV transmission clusters in some
areas[9,10]
6. Witt MD, et al. Clin Infect Dis. 2013;57:77-84. 7. Wandeler G, et al. Clin Infect Dis. 2012;55:1408-1416.
8. Lea T, et al. Sexual Health. 2013;10:448-451. 9. Urbanus AT, et al. AIDS. 2009;23:F1-F7.
10. MMWR. 2011;60:945-950.
9. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Risk Factors for Sexual HCV Transmission
Among HIV+ MSM
Multiple factors associated with HCV transmission[11,12]
– Unprotected receptive anal intercourse
– Online casual sexual partners
– Sex at sex venues
– Older age
– Syphilis
– Recreational drug use
– Drinking > 13 alcoholic drinks per week
11. Witt MD, et al. Clin Infect Dis. 2013;57:77-84. 12. Larsen C, et al. PLoS ONE. 2011;6:e29322.
11. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Screening, Surveillance, Treatment
Initiation for HCV in HIV+ Patients
US and international treatment guidelines recommend[13-
16]:
– HCV screening at HIV diagnosis, then annually and as
indicated
– More frequent surveillance if ongoing risk (eg, MSM, IDU)
– HCV RNA if HCV Ab+ or suspected acute infection
13. EACS Guidelines, Version 7.0. October 2013. 14. DHHS Antiretroviral Guidelines for Adults and
Adolescents. February 2013. 15. Brook G, et al. HIV Med. 2010;11:1-30. 16. Ghany MG, et al. Hepatology.
2009;49:1335-1374.
13. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Why Is HCV Therapy Deferred in Many
HIV/HCV-Coinfected Patients?
Challenges with interferon- and/or ribavirin-based regimen
Anticipated approval of new agents
– Greater efficacy
– All-oral regimens
– Shorter duration
– Improved tolerability
– Fewer drug-drug interactions
14. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Challenges With Telaprevir- or Boceprevir-
Based HCV Therapy in Coinfected Patients
Regimen complexity[17,18]
– High pill burden
– Long duration, complex RGT rules
– Multiple drug-drug interactions
– Overlapping toxicities
– With/without food dosing requirements
Tolerability
– Additional AEs beyond peginterferon/ribavirin
17. Taylor LE, et al. Clin Infect Dis. 2012;55(suppl 1):S33-S42. 18. DHHS Antiretroviral Guidelines for
Adults and Adolescents. February 2013.
15. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Specific Risks of Deferring Therapy in
HIV/HCV-Coinfected Patients
Accelerated rate of HCV-related hepatic fibrosis
progression in coinfected patients with increasing immune
deficiency[19-22]
– Progression to cirrhosis risk 3-fold higher in coinfected vs
HCV-monoinfected patients[20]
– Relative risk of decompensated liver disease 6-fold higher in
coinfected vs HCV-monoinfected patients[21]
Coinfected patients have reduced access to liver
transplantation and reduced survival
19. Taylor LE, et al. Clin Infect Dis. 2012;55(suppl 1:S33-42). 20. DHHS Antiretroviral Guidelines for
Adults and Adolescents. February 2013. 21. Naggie S, et al. Gastroenterology. 2012;142:1324-1334.
22. Macías J, et al. Clin Infect Dis. 2013;57:1401-1408.
16. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
HCV Coinfection vs Monoinfection:
Cumulative Incidence of Decompensation
10-year hepatic decompensation risk 83% higher in coinfected
patients
– Adjusted HR 1.83 (95% CI: 1.54-2.18)
P < .001
HIV/HCV coinfected
HCV monoinfected
0.074
0.048
23. Lo Re V, et al. IAC 2012. Abstract WEAB0102.
0
0.1
0.2
0 1 2 3 4 5 6 7 8 9 10
Yrs to Hepatic Decompensation
17. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Importance of Informed Deferral:
Know What You Are Waiting for
Need for individualized decision-making and informed
consent
Stepwise progress in HCV therapy anticipated
– New interferon-based regimens
– All-oral regimens retaining ribavirin
– All-oral regimens of just DAAs
Uncertain timeline
Initial DAA studies excluded coinfected patients
18. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Assessing HIV+ Patients for Immediate or
Deferred HCV Therapy
Antiretroviral therapy for HIV treatment-naive HIV/HCV-
coinfected patients
– CD4+ cell count < 500 cells/mm3: initiate antiretroviral
therapy for HCV treatment optimization[24,25]
– CD4+ cell count > 500 cells/mm3: may defer antiretroviral
therapy until HCV therapy completed[25]
24. EACS Guidelines, Version 7.0. October 2013. 25. DHHS Antiretroviral Guidelines for Adults and
Adolescents. February 2013. 26. Macías J, et al. Clin Infect Dis. 2013;2013;57:1401-1408.
HCV Therapy in HIV/HCV-Coinfected, HCV Treatment-Naive Patients
Liver Fibrosis
Consider
HCV Therapy
Eligible to
Defer HCV Therapy
No/minimal fibrosis (F0-F2)[24,25] ●
Advanced fibrosis (F3-F4); cirrhosis[26] ●
20. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
SVR With PegIFN/RBV by Genotype:
Coinfection vs Monoinfection
27. Carrat F, et al. JAMA. 2004;292:2839-2848. 28. Laguno M, et al. Hepatology. 2009;49:22-31. 29.
Chung RT, et al. N Engl J Med. 2004;351:451-459. 30. Torriani FJ, et al. N Engl J Med. 2004;351:438-450.
31. Núñez M, et al. AIDS Res Hum Retroviruses. 2007;23:972-982. 32. Peginterferon alfa 2a [package
insert].
SVR Range, %
HIV/HCV Coinfection HCV Monoinfection
GT1 or
GT4[27-31]
GT2 or
GT3[27-31]
GT1 or
GT4[32]
GT2 or
GT3[32]
PegIFN/RBV
(600-1200 mg)
14-35 44-73 0-82* 76-82
*SVR rates for GT1 or GT4 unaffected by baseline viral titer. PegIFN/RBV for 48 weeks
using 1000 mg or 1200 mg dose of pegIFN resulted in higher rates of SVR compared
with 24 weeks of therapy and/or 800 mg dose of pegIFN.
21. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Proposed Optimal Duration of PegIFN/RBV
Therapy in Coinfected Patients
33. EACS Guidelines, Version 7.0. October 2013.
*In patients with baseline low viral load and
minimal liver fibrosis.
**Where no access to DAA available or high
chances of cure even with dual therapy
(favorable IL28B genotype, low HCV viral
load, and no advanced fibrosis).
HCV RNA
negative
Wk 4 Wk 12 Wk 24 Wk 48 Wk 72
GT2/3
GT1/4**
Stop
Stop
GT2/3
GT1/4
24-wk
therapy*
48-wk
therapy
72-wk
therapy
HCV RNA
positive
HCV RNA
negative
HCV RNA
positive
> 2 log drop
in HCV RNA
< 2 log drop
in HCV RNA
22. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Study 110: Telaprevir + PegIFN/RBV in
GT1 HCV/HIV Coinfection
Phase II randomized controlled
trial[34]
– Telaprevir TID + pegIFN/RBV vs
pegIFN/RBV alone for 48 weeks
HCV treatment-naive HIV+ patients
(N = 60)
No HIV breakthrough
Safety and tolerability
– Increased pruritus, headache,
nausea, rash, and dizziness with
telaprevir-based therapy
– Anemia: 18% in both groups
SVR comparable to GT1 HCV-
monoinfected patients (75%)[35]
No ART
EFV/TDF/FTC
ATV/ritonavir
+ TDF/FTC
Total
SVR(%)
n/N = 5/
7
11/
16
12/
15
28/
38
Telaprevir +
PegIFN/RBV
PegIFN/RBV
2/
6
4/
8
4/
8
10/
22
34. Sulkowski MS, et al. Ann Intern Med. 2013;159:86-96.
35. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
100
80
60
40
20
0
71 69
80
74
33
50 50
45
23. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Study P05411: Boceprevir + PegIFN/RBV
in GT1 HCV/HIV Coinfection
Phase II randomized controlled
trial[36]
– PegIFN/RBV lead-in 4 weeks then
boceprevir + pegIFN/RBV for 44
weeks vs pegIFN/RBV alone for 48
weeks
HCV treatment-naive HIV+ patients
(N = 98)
– All with HIV-1 RNA < 50 cells/mL
on antiretroviral therapy
No difference in HIV breakthrough
Safety and tolerability
– Increased anemia, pyrexia, and
decreased appetite with boceprevir-
based therapy
SVR comparable to GT1 HCV-
monoinfected patients (68%)[37]
0
20
40
60
80
100
SVR(%)
PegIFN/RBV
n/N = 10/34
29
40/64
63
Boceprevir +
PegIFN/RBV36. Sulkowski M, et al. Lancet Infect Dis. 2013;13:597-605.
37. Poordad F, et al. N Engl J Med. 2011;364:1195-1206.
24. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Recommendations for Coadministration of
TVR and BOC With Select Antiretroviral Agents
Antiretroviral Agent
Telaprevir Boceprevir
Europe[38-40] US[41] Europe[38-40] US[41]
Atazanavir/ritonavir
Monitor for
hyperbilirubinemia
Standard dose
Case-by-case
consideration
Do not use
Darunavir/ritonavir;
fosamprenavir/ritonavir
; lopinavir/ritonavir
Not
recommended
Not
recommended
Not
recommended
Not
recommended
Raltegravir
No dose
adjustment
No dose
adjustment
No dose
adjustment
No dose
adjustment
Efavirenz
Increase dose
(1125 mg q8h)
Increase dose
(1125 mg q8h)
Not
recommended
Do not use
Rilpivirine
No dose
adjustment
No guidance
No dose
adjustment
No dose
adjustment[44]
38. Telaprevir [EU package insert]. 39. Boceprevir [EU package insert]. 40. Kakuda TN, et al. IWCPHT 2012. Abstract O-18. 41.
DHHS Antiretroviral Guidelines for Adults and Adolescents. February 2013. 42. Simeprevir [package insert]. 43. Sofosbuvir
[package insert]. 44. Boceprevir [package insert].
Note: Telaprevir and boceprevir interact with CYP3A4/5 and p-glycoprotein. Simeprevir should not be
coadministered with any boosted or unboosted PI or any NNRTI except rilpivirine.[42] Sofosbuvir has no
reported DDIs with HIV drugs except tipranavir/ritonavir.[43]
26. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Advantages of Future HCV Therapies
Once-daily dosing
Shorter duration
Simpler regimens—no response-guided therapy
Fewer adverse events
Interferon-free
High efficacy
27. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Caveats to Future HCV Therapies
Clinical trial data in HIV/HCV coinfection still emerging
– DDI data incomplete
– Performance outside select trial populations yet to be seen
Timeline
– Late 2013: FDA approval of simeprevir (GT1) and sofosbuvir
(GT1-4)
– 2014: anticipated FDA approval of faldaprevir (GT1);
first all-oral regimens for GT1 expected to be approved
Costs uncertain, but likely an issue in many regions
28. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
C212 Study: Simeprevir + PegIFN/RBV in
GT1 HCV/HIV Coinfection
Phase III randomized controlled
trial[45]
– 24- or 48-week regimens: SPV +
pegIFN/RBV for 12 weeks, then
pegIFN/RBV alone
HCV treatment-naive or -
experienced HIV+ patients
(N = 106)
– 88% on ART (VL < 50 cells/mL)
– Excluded: boosted PIs,
NNRTIs other than RPV
Safety profile similar to
monoinfected pts
– Pruritus and photosensitivity in
20% and 2%, respectively
SVR comparable to GT1 HCV-
monoinfected pts (80%)[46]
7/
10
16/
28
100
80
60
40
20
0
SVR12(%)
78/
106
74
Overall
70
42/
53
79
Naive
57
13/
15
87
Relapsers
n/N =
Partial Null
45. Dieterich D, et al. EACS 2013. Abstract LBPS9/5. 46. Jacobson I, et al. EASL 2013. Abstract 1425.
29. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
PHOTON-1: Sofosbuvir + RBV in GT1/2/3
HIV/HCV Coinfection
Phase III open-label study
– 12- (GT2/3 treatment-naive) or 24-
week regimens (GT1 treatment-
naive, GT2/3 treatment
experienced): sofosbuvir + RBV
HCV treatment-naive or -
experienced HIV+ patients
(N = 223)
– Approx 76% on ART (VL < 50
cells/mL), various standard
regimens
Safety profile similar to
monoinfected patients; consistent
with RBV
– Most frequent AEs: fatigue,
insomnia, headache, nausea,
diarrhea
2 patients had transient HIV
rebound due to nonadherence
47. Sulkowski MS, et al. AASLD 2013. Abstract 212.
n/N
87/
114
Virologic Outcomes for
Treatment-Naive Patients
by GT
76
88
67
0
20
40
60
80
100
GT1 GT2 GT3
SVR12(%)
23/
26
28/
42
30. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
STARTVerso4: Faldaprevir + PegIFN/RBV
in GT1 HCV/HIV Coinfection
Phase III open-label study
– 24- or 48-week regimens:
faldaprevir + pegIFN/RBV for 12 or
24 weeks, then pegIFN/RBV alone
HCV treatment-naive or previous
relapser HIV+ patients (N = 308)
– 96% on ART (VL < 50 cells/mL)
Safety profile similar to
monoinfected pts
– Most frequent AEs: nausea, fatigue,
diarrhea, headache
– Decrease in hemoglobin consistent with
pegIFN/RBV historical data
1 patient had HIV rebound requiring
new ART regimen
*24 wks of therapy; †12 wks of therapy
49. Rockstroh JK, et al. AASLD 2013. Abstract 1099.
72
79
84
0
20
40
60
80
100
Faldaprevir
120 mg*
Faldaprevir
240 mg†
Faldaprevir
240 mg*
n/N =
89/
123
66
84
72/
86
SVR4(%)
32. clinicaloptions.com/hepatitis
Best Practices in the Management of HCV/HIV Coinfection
Summary
Liver disease leading cause of morbidity and mortality in
HIV/HCV coinfection
– Antiretroviral therapy may slow progression
HCV screening at HIV diagnosis and at least annually
HCV treatment considerations
– Treat now or wait for future options?
– First-generation DAAs complex, long duration, AEs, DDIs
– New agents may improve outcomes with shorter therapy,
fewer AEs
– Consider HCV disease stage and risk of progression